Research articles
ScienceAsia 49 (2023):ID 717-725 |doi:
10.2306/scienceasia1513-1874.2023.069
Sphingosine 1-phosphate suppresses the viability and
estradiol secretion of mouse granulosa cells by activating
Gα12/13-YAP signaling
Xiaoling Fua, Shuangshuang Liangb,*
ABSTRACT: Polycystic ovary syndrome (PCOS) is a disease with abnormal hormones affecting 6?8% of women in
reproductive age. Accumulating evidence supports the critical role of sphingosine 1-phosphate (S1P), a biologically
active lipid, in PCOS mechanisms. Downstream of S1P, the G protein-coupled receptor (GPCR) family member
S1PRs transduce the signal to the Hippo/yes-associated protein 1 (YAP) signal axis which might be involved in the
survival, growth, and death of ovarian granulosa cells (GCs), which let us suppose whether S1P contributes to the
development of PCOS by regulating G?12/13-YAP signaling in GCs. This study was designed to examine the action of
the S1P/GPCR/YAP signal axis on GCs with a focus on estrogen response of cell viability. The distribution of all S1PRs
in mouse ovarian GCs was determined, and it was found that S1PR2 exhibited the strongest expression. In GCs, S1P
inhibited YAP phosphorylation at Ser127 and promoted YAP translocation from cytosol to the nucleus. S1P attenuated
viability of GCs through activating YAP from G?12/13 under GPCR activation, which was restored by excessive ?estradiol, indicating the role of S1P/GPCR/YAP signal in estrogen response. Furthermore, S1P also activated YAP to
suppress the secretion of estrogen from GCs. The findings presented here provide an inviting therapeutic option for
PCOS which involves the dysfunction of GCs.
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a |
Department of Endocrinology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine,
Hubei 430015 China |
b |
Department of Obstetrics and Gynecology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine,
Hubei 430015 China |
* Corresponding author, E-mail: lshuang2004@163.com
Received 17 Oct 2022, Accepted 27 Jun 2023
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